Kinetin (N6-furfuryladenine) (CAS #525-79-1) is a derivative of adenine which is one of the nucleic acid purine bases, and it belongs to the cytokinin group of plant growth hormones. Kinetin is an amphoteric compound which is soluble in strong acids, alkalis, and glacial acetic acid, is slightly soluble in ethanol, butanol, acetone and ether, but is practically insoluble in distilled water. Although the exact mechanisms of action of kinetin are yet to be revealed, various lines of evidence indicate that kinetin is involved in signal transduction and also acts as a natural antioxidant. Since 1994, kinetin has been thoroughly tested for its powerful anti-aging effects in human skin cells and other systems.
Zeatin ((E)-2-methyl-4-(7H-purin-6-ylamino)but-2-en-1-ol) (CAS #1637-39-4), a plant hormone and derivative of adenine, was originally purified from immature kernels of the corn Zea mays, and was later identified to be present in the tRNA of a wide variety of organisms. It has been known to promote maintenance of small cell size (a key determinant of youthful skin) and structural and functional integrity of cells. Zeatin exists in two forms, trans and cis. The activity of zeatin is attributed to its more stable trans form.
At present, kinetin and zeatin are widely used components in numerous skin care cosmetic therapies, such as Kinerase® and ProTherapy MD® (Valeant Pharmaceuticals International Inc., Bridgewater, N.J.). Kinetin and zeatin each has been used in cosmetic formulations at concentrations up to 0.2% for kinetin and up to 0.1% for zeatin. Kinetin and zeatin, in addition to being practically insoluble in water, are very difficult to solubilize in solvents suitable for use in cosmetic formulations at meaningful concentrations. Unfortunately, extensive evaluations have failed to identify a cosmetic ingredient with good solubilizing capacity for kinetin, zeatin, or both in combination
Hydrophilic penetration enhancing agents that improve the solubility of a drug in water, such as Transcutol® (Gattefosse, St. Priest, France), propylene glycol, polyethylene glycol, and Labrasol® (Gattefosse), have been used to increase the penetration of a drug that is solubilized within a liposome. As reported in Chessa et al., Pharmaceutics, 3:497-509 (2011), the inclusion of such hydrophilic agents in a formulation in which the drug is solubilized within a liposome has no deleterious effect on the solubility of the drug in the formulation with the addition of water.
The effectiveness of topical pharmaceutical agents such as kinetin and zeatin can be enhanced when the amount of the agent that is dissolved, relative to the amount that is in suspension, in a formulation is increased. Moreover, the effectiveness of topical cosmetic and pharmaceutical agents is generally enhanced by the use of agents that increase penetration of the agents into skin. Water is a desirable vehicle for topical formulations because, unlike organic solvents, water does not dry the skin or irritate damaged skin. However, because water is a poor solvent for kinetin and zeatin, a significant need exists for a solution to the problem of increasing the solubility of kinetin and/or zeatin in pharmaceutical formulations that contain water as a major ingredient.